Japan today is showing extraordinary interest in India and nothing reflects this more strongly than Prime Minister Shinzo Abe's visit to New Delhi in August. Moreover, Abe is the third successive Japanese prime minister to make such a visit and, starting this year, India is the only country with which Japan will conduct annual talks at the prime ministerial level.

Abe hewed to his foreign visits schedule and made a week-long trip to Indonesia, India and Malaysia – beginning 19 August despite political uncertainties in Japan and his weakened position as prime minister following the Liberal Democratic Party's dismal performance at the July House of Councillors elections. Recognising strategic competition for energy security, Abe signed a bilateral free trade agreement with Indonesia, the largest supplier of liquefied natural gas to Japan. In return Japan guaranteed Indonesia liberal access to its markets for a range of Indonesian products including farm produce – rice exempted.

The on-body flow and near-to-intermediate wake of a 6:1 prolate spheroid at a pitch angle of $\alpha = 10^{\circ }$ and a length-based Reynolds number, ${Re}_L = U_\infty L / \nu = 3 \times 10^4$, are investigated using large eddy simulation (LES) across four stratification levels: ${\textit {Fr}} = U_{\infty }/ND = \infty , 6, 1.9$ and $1$. A streamwise vortex pair, characteristic of non-zero $\alpha$ in unstratified flow over both slender and blunt bodies, is observed. At ${\textit {Fr}} = \infty$ (unstratified) and $6$, the vortex pair has a lateral left–right asymmetry as has been reported in several previous studies of unstratified flow. However, at higher stratification levels of ${\textit {Fr}} = 1.9$ and $1$, this asymmetry disappears and there is a complex combination of body-shed vorticity that is affected by baroclinicity and vorticity associated with internal gravity waves. Even at the relatively weak stratification of ${\textit {Fr}} = 6$, the wake is strongly influenced by buoyancy from the outset: (a) the vertical drift of the wake is more constrained at ${\textit {Fr}} = 6$ than at ${\textit {Fr}} = \infty$ throughout the domain; and (b) the streamwise vortex pair loses coherence by $x/D = 10$ in the ${\textit {Fr}} = 6$ wake, unlike the ${\textit {Fr}} = \infty$ case. For the ${\textit {Fr}} = 1$ wake, flow separation characteristics differ significantly from those at ${\textit {Fr}} = \infty$ and $6$, resulting in a double-lobed wake topology that persists throughout the domain.

Thyroid disorders are increasingly prevalent globally and are considered metabolic-lifestyle diseases. While medications can manage thyroid dysfunction, they are usually lifelong, costly, and not always practical. Intermittent fasting (IF), a highly adaptable dietary regimen, has been shown to influence lifestyle, gut microbiome, and circadian rhythms. Our study hypothesized that IF, combined with vitamin supplementation, could reduce the risk of thyroid disorders due to their antioxidant effects. In this study, experimental animals were divided into five groups: Euthyroid, hypothyroidism control, IF + vitamin E, vitamin E, and IF. Hypothyroidism was induced using propylthiouracil (PTU) over 24 days, and IF and vitamin E (66 mg/ml) were administered based on the experimental group. The hypothyroid animals exhibited increased anxiety, weight gain, lipid peroxidation, and a significant reduction in thyroid hormone levels, locomotor activity, and antioxidant levels—clear signs of thyroid dysfunction’s impact on metabolism and overall health. Our proposed therapies IF and vitamin E effectively mitigated thyroid damage. Drawing inspiration from ancient Ayurveda and modern healthcare strategies, these cost-effective and practical regimens offer a promising solution to managing thyroid disorders globally.

Objectives/Goals: Colorectal cancer (CRC) is classified into right-sided, left-sided, and rectal cancer. Clinicopathological and molecular features vary along the colorectum, even within subsites, leading to inconsistencies in identifying relevant biomarkers. We created a CRC metabolome map to explore diagnostic and survival heterogeneity across subsites. Methods/Study Population: A total of 372 patient-matched tumor and normal tissue samples were collected from seven colorectal subsites: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92). Liquid chromatography–mass spectrometry was used to compare metabolite abundances. Cox proportional hazards regression assessed metabolite impact on survival, adjusted for clinical covariates. Parametric and nonparametric tests were applied to compare the metabolite abundances. An interactive, publicly accessible online platform was developed to allow researchers to explore and generate hypotheses from this data. Results/Anticipated Results: Our study identified 39 and 70 significantly altered metabolites, including bile acids and lysophosphatidylcholines, across tumors and normal mucosa, showing metabolic heterogeneity between CRC subsites. We observed significant linear trends in metabolite gradients from the cecum to the rectum, and it was depended on the disease status. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite. Metabolite differences correlated with survival were unique to each subsite. Additionally, we developed an interactive, publicly accessible CRC metabolome database to share this valuable resource: https://colorectal-cancer-metabolome.com/yale-university. Discussion/Significance of Impact: This study provides the first CRC metabolome map, revealing metabolic differences across colorectal subsites. It challenges the right vs. left CRC classification, highlighting subsite-specific biomarker identification. Findings offer insights for personalized treatments tailored to the tumor type to improve patient outcomes.

Objectives/Goals: Immune checkpoint inhibitors (IO) have dramatically improved survival outcomes in patients with metastatic melanoma. Still, many patients do not respond these treatments, and others may experience harmful adverse events (irAEs). Thus, there an unmet need for biomarkers for real-time monitoring and management of patients exposed to IO therapies. Methods/Study Population: Serial serum samples were collected from patients with BRAFV600-mutant metastatic melanoma treated with ipilimumab/nivolumab (IO, n = 14) or dabrafenib/trametinib (TT, n = 10). Methylated cell-free DNA (cfDNA) was isolated and sequenced using enzymatic methyl-seq. We develop a robust computational pipeline to identify the top 250 cell-type specific regions of differential methylation (DMRs) across 24 cell-types. Using these differentially methylated regions, a deconvolution tool was developed to determine the abundance of cell type-specific cfDNA in patient serum, and changes in abundance were tracked over treatment time-course to assess response treatment and identify signals of adverse events. Results/Anticipated Results: We demonstrated improved precision in DMR detection evidenced by a higher area under the receiver operator characteristic curve (AUROC) of 0.85 on average. Pathway and functional annotation analysis revealed melanocyte-specific methylation marker regions regulated genes related to melanocyte development and differentiation, including MITF, SOX9/10, and FOXD3. We show these regions are conserved through the transformation to malignant melanoma, indicating melanocyte cfDNA abundance can be used as a marker for tumor burden. We characterize the dynamics of melanocyte-derived cfDNA over the course of treatment in responders and nonresponders to both IO and TT. We observe that changes in concentrations of cfDNA from other cell types correlate with clinically observed irAE-mediated damage to normal tissue. Discussion/Significance of Impact: We demonstrated the utility of decoding the origins of cfDNA fragments obtained from serial liquid biopsy samples. Using cell-specific methylation marks, we identified a signature from the primary melanoma to assess response to treatment, while also obtaining a signal from other tissues throughout the body to monitor immune related adverse events.

This paper contributes to an underdeveloped yet critical feature of international criminal law – victim assistance. With the creation of the ICC and the Trust Fund for Victims, the idea of victim assistance in situations of mass criminalities was provided an institutional backbone. However, much of its operational principles remain theoretically ill-defined. Through a methodological study of over a decade of assistance programmes administered by the Fund, this paper sheds light on some of the critical operational principles which have emerged in practice. Additionally, in light of these principles, this paper argues that there exist two major causes of ineffectiveness which hamper the Fund’s assistance work – first, the problem of defining its goals in definite, strategic terms, and second, the overlap between assistance mandate of the Fund and reparations regime of the ICC. It concludes by making course-correction suggestions for the Fund to chart a future towards an effective organization building.

A co-relation between Schistosoma japonicum (Sj) and liver cancer (LC) in humans has been reported in the literature; however, this association is circumstantial. Due to the inconclusive nature of this association, the International Agency for Research on Cancer has placed Sj in Group 2B for LC, signifying it to be a ‘possible carcinogen’. Many epidemiological, pathological and clinical studies have identified multiple factors, linked with Sj infection, which can lead to liver carcinogenesis. These factors include chronic inflammation in response to deposited eggs (which leads to fibrosis, cirrhosis and chromosomal instability at cellular level), hepatotoxic effects of egg-antigens, co-infection with hepatitis viruses, and up-regulation of glycolysis linked genes among others which predisposes hepatic tissue towards malignant transformation. The objective of this work is to present the current understanding on the association of Sj infection with LC. Mechanisms and factors linked with Sj infection that can lead to LC are emphasized, along with measures to diagnose and treat it. A comparison of liver carcinogenesis is also provided for cases linked with and independent of Sj infection. It appears that Sj, alone or with another carcinogen, is an important factor in liver carcinogenesis, but further studies are warranted to conclusively label ‘infection with Sj alone’ as a liver carcinogen.

We use an experiment to examine whether form of payment (cash or mobile money) affects estimates of intertemporal choice and risk taking. We find that form of payment does not affect temporal discounting and risk taking. Given that participants prefer payment via mobile money, the results suggest that there are minimal concerns with using mobile money to pay participants in experimental studies.

The incidence of Kawasaki Disease has a peak in the winter months with a trough in late summer/early fall. Environmental/exposure factors have been associated with a time-varying incidence. These factors were altered during the COVID-19 pandemic. The study was performed through the International Kawasaki Disease Registry. Data from patients diagnosed with acute Kawasaki Disease and Multiple Inflammatory Syndrome-Children were obtained. Guideline case definitions were used to confirm site diagnosis. Enrollment was from 1/2020 to 7/2023. The number of patients was plotted over time. The patients/month were tabulated for the anticipated peak Kawasaki Disease season (December–April) and non-peak season (May–November). Data were available for 1975 patients from 11 large North American sites with verified complete data and uninterrupted site reporting. The diagnosis criteria were met for 531 Kawasaki Disease and 907 Multiple Inflammatory Syndrome-Children patients. For Multiple Inflammatory Syndrome-Children there were peaks in January of 2021 and 2022. For Kawasaki Disease, 2020 began (January–March) with a seasonal peak (peak 26, mean 21) with a subsequent fall in the number of cases/month (mean 11). After the onset of the pandemic (April 2020), there was no clear seasonal Kawasaki Disease variation (December–April mean 12 cases/month and May–November mean 10 cases/month). During the pandemic, the prevalence of Kawasaki Disease decreased and the usual seasonality was abolished. This may represent the impact of pandemic public health measures in altering environmental/exposure aetiologic factors contributing to the incidence of Kawasaki Disease.

Growth differentiation factor 9 (GDF9) is an oocyte-specific paracrine factor involved in bidirectional communication, which plays an important role in oocyte developmental competence. In spite of its vital role in reproduction, there is insufficient information about exact transcriptional control mechanism of GDF9. Hence, present study was undertaken with the aim to study the expression of basic helix-loop-helix (bHLH) transcription factors (TFs) such as the factor in the germline alpha (FIGLA), twist-related protein 1 (TWIST1) and upstream stimulating factor 1 and 2 (USF1 and USF2), and nuclear receptor (NR) superfamily TFs like germ cell nuclear factor (GCNF) and oestrogen receptor 2 (ESR2) under three different in vitro maturation (IVM) groups [follicle-stimulating hormone (FSH), insulin-like growth factor-1 (IGF1) and oestradiol)] along with all supplementation group as positive control, to understand their role in regulation of GDF9 expression. Buffalo cumulus–oocyte complexes were aspirated from abattoir-derived ovaries and matured in different IVM groups. Following maturation, TFs expression was studied at 8 h of maturation in all four different IVM groups and correlated with GDF9 expression. USF1 displayed positive whereas GCNF, TWIST1 and ESR2 revealed negative correlation with GDF9 expression. TWIST1 & ESR2 revealing negative correlation with GDF9 expression were found to be positively correlated amongst themselves also. GCNF & USF1 revealing highly significant correlation with GDF9 expression in an opposite manner were found to be negatively correlated. The present study concludes that the expression of GDF9 in buffalo oocytes remains under control through the involvement of NR and bHLH TFs.

We describe our experience implementing an intensive quality improvement cohort pilot focused on managing asymptomatic bacteriuria in 19 critical access hospitals. Participation in the pilot was high, and almost all sites identified an improvement goal and collected clinical data. Barriers to implementation included staffing shortages, turnover, and lack of bandwidth.

Eight major supply chains contribute to more than 50% of the global greenhouse gas emissions (GHG). These supply chains range from raw materials to end-product manufacturing. Hence, it is critical to accurately estimate the carbon footprint of these supply chains, identify GHG hotspots, explain the factors that create the hotspots, and carry out what-if analysis to reduce the carbon footprint of supply chains. Towards this, we propose an enterprise decarbonization accelerator framework with a modular structure that automates carbon footprint estimation, identification of hotspots, explainability, and what-if analysis to recommend measures to reduce the carbon footprint of supply chains. To illustrate the working of the framework, we apply it to the cradle-to-gate extent of the palm oil supply chain of a leading palm oil producer. The framework identified that the farming stage is the hotspot in the considered supply chain. As the next level of analysis, the framework identified the hotspots in the farming stage and provided explainability on factors that created hotspots. We discuss the what-if scenarios and the recommendations generated by the framework to reduce the carbon footprint of the hotspots and the resulting impact on palm oil tree yield.

The relationship between Schistosoma mansoni (Sm) and hepatocellular carcinoma (HCC) has been evaluated by many studies that point towards a co-relation between schistosomal infection and HCC. While many such studies demonstrated that Sm infection in the presence of another carcinogenic factors leads to HCC, none of these studies could conclusively prove the cancer-inducing ability of Sm in humans, independent of other carcinogenic factors. The aim of this work is to present the current understanding on the association of Sm with HCC. Many epidemiological, pathological, and clinical studies have shown the role of multiple events like chronic inflammation and fibrosis as well as hepato-toxic agents like soluble egg antigens (SEAs), which help in creating a micro-environment which is suitable for HCC development. The role of Sm infection and deposited eggs in causing persistent inflammation, advanced fibrosis, and the role of SEAs, especially IPSE/alpha-1, is emphasised. This work concludes that Sm infection has the potential to induce cancer independently but the same has not been reported in humans to date. Extensive research is required to establish a causal relationship between Sm infection and HCC induction, or a complete lack thereof. However, Sm infection definitely acts along with other carcinogenic factors to induce HCC at a much faster pace and also leads to an aggressive form of liver cancer, which the other carcinogenic factor could not have achieved alone.

We study piecewise injective, but not necessarily globally injective, contracting maps on a compact subset of ${\mathbb R}^d$. We prove that, generically, the attractor and the set of discontinuities of such a map are disjoint, and hence the attractor consists of periodic orbits. In addition, we prove that piecewise injective contractions are generically topologically stable.